We have previously identified two BCGF II-like factors found in a human BCGF and murine D10T cell sup, which can be distinguished by their differential reactivity in several murine BCGF II assays. Extending the characterization of these two factors, we showed that when they were simultaneously added to culture, they synergized to produce optimal IgM secretion by large murine B cells and murine BCL1 B lymphoma cells. The same factors were tested in an IgM specific plaque assay and a similar synergistic response was observed for the large B cells, but not for the BCL1 cells. Kinetic analysis of the time of action of the two BCF II-like lymphokines in the induction of the PFC response by large B cells indicated that human BCGF was required within the first 24 hours of a 4 day culture period, while D10 sup could be added as late as the final 15 hours without significant diminution of the response. These data provide further support for the existence of two distinct B cell stimulatory factors which cause growth and differentiation of activated B cells, and indicate that these two factors synergize to produce optimal Ig secretion.